3 - Action potentials & receptors

Question 1

Voltage-gated ion channels

Answer 1

• Embedded in the plasma membrane of the neuron are ion channels that are sensitive to the voltage of the cell
• These channels open only when the voltage in the cell reaches a certain value
• These are termed voltage-gated ion channels

Question 2

Voltage-gated Na+ channels

Answer 2

• Have both an activation gate and an inactivation gate.

- At rest, the activation gate is closed and the inactivation gate is open

Question 3

Voltage-gated K+ channels

Answer 3

• Have one activation gate, which opens to allow the flow of K+ ions through the channel and closes to stop the flow of K+ ions

Question 4

Neuron at rest

Answer 4

When the membrane potential is -70mV, voltage-gated Na+ channels are closed and the concentration of Na+ outside the cell is higher than inside the cell

Question 5

Initial stimulation

Answer 5

• When the neuron receives an excitatory signal or stimulus, ligand-gated ion Na+ channels open
• Small amounts of Na+ will move down their concentration gradient into the neuron and the resting potential will start to become more positive

Question 6

Depolarisation

Answer 6

• Once the membrane potential reaches a critical threshold of -55 mV, voltage-gated activation gates in the Na+ channel open quickly, allowing Na+ to flood into the neuron
• As a result of the large influx of positively charged Na+ the neuron quickly loses its negative charge and undergoes depolarisation

Question 7

Inactivation of Na+ channels

Answer 7

When the inside of the neuron become highly positive, the pore of the voltage-gated Na+ channels is plugged by the inactivation gate and the flow of Na+ into the neuron stops

Question 8

Repolarisation

Answer 8

• Eventually the intracellular environment of the neuron becomes sufficiently positive that voltage-gated K+ channels begin to open slowly
• Opening of these channels allows K+ to flow down its concentration gradient out of the cell
• This movement of K+ causes the inside of the neuron to quickly regain its negative charge in a process called repolarisation

Question 9

Hyperpolarisation

Answer 9

• In response to the increasingly negative charge inside the neuron, the voltage-gated K+ channels close.
Because this process is slow, some K+ ions continue to move outside the cell while the channel is closing
• This extra efflux of K+ causes the membrane potential to become more negative than the resting potential of -70 mV. This process is called hyperpolarisation

Question 10

Refractory period

Answer 10

• During the period of hyperpolarization, the neuron will not be able to fire another action potential. This is termed the refractory period
• Eventually, the action of the Na+/K+ ATPase pump will restore the resting membrane potential to -70mV and the neuron will be ready to fire another action potential

Question 11

Action potential overview

Answer 11

1. Resting state
2. Threshold
3. Depolarization phase of the action potential
4. Repolarizing phase of the action potential
5. Undershoot

Question 12

Benefit of the action potential

Answer 12

A single action potential takes only milliseconds to complete, enabling the neuron to fire quickly in response to the hundreds of signals it receives every second

Question 13

Action potential initiation

Answer 13

Action potentials are initiated at the base of the neuron in the region called the axon hillock

Question 14

Action potential movement

Answer 14

• The action potential will be transmitted down the axon
• Small gaps in the myelin, called nodes of Ranvier, allow ion movement across the axon membrane at these sites through saltatory conduction

Question 15

Saltatory conduction

Answer 15

When the action potential to ‘jumps’ from one node to another, thereby allowing the signal to be transmitted very quickly.

Question 16

Propagation of an action potential along an unmyelinated axon

Answer 16

1. As an action potential develops in the initial segment, the transmembrane potential depolarizes to +30mv
2. A local current depolarizes the adjacent portion of the membrane to threshold
3. An action potential develops at this location, and the initial segment enters the refractory period
4. A local current depolarizes the adjacent portion of the membrane to threshold, and the cycle is repeated.

Question 17

properties of action potentials

Answer 17

• An action potential will not be triggered if the excitatory stimulus does not raise the membrane potential to the threshold potential
• Action potentials are “all or none” – they either fire or they do not
• Information is coded by the frequency of the firing of action potentials (i.e. the number of spikes over a given period of time), rather than the size of the action potential, which is always the same

Question 18

electrical synapses

Answer 18

use gap junctions that directly connect the cytoplasm between 2 cells

Question 19

chemical synapses

Answer 19

involve the release of neurotransmitters from a pre-synaptic neuron that diffuse across the synaptic cleft & bind to post-synaptic neurons
• Chemical synapses are the most common type

Question 20

Synaptic vesicles

Answer 20

Store neurotransmitter

Question 21

quantum

Answer 21

amount of neurotransmitter in 1 vesicle

Question 22

Physiology of a chemical synapse

Answer 22

• Arrival of action potential causes influx of Ca2+ and fusion of vesicles with pre-synaptic membrane and release of transmitter into synaptic cleft
• Transmitter binds to receptor on post-synaptic membrane
• End of transmitter activity via
  i) catabolism (degradation)
  ii) Uptake of transmitter into axon terminal or glial cells

Question 23

Summary of signalling at a chemical synapse

Answer 23

• When the depolarization of the action potential reaches the presynaptic terminal, the voltage-gated Ca2+ ion channels open.
• In response to the increase in intracellular Ca2+, vesicles containing neurotransmitter fuse with the plasma membrane of the neuron. This causes the neurotransmitter to be released into the synapse.
• Neurotransmitter diffuses across the synapse and binds to receptors on the postsynaptic neuron. For excitatory neurotransmitters, this causes Na+ ion channels to open and entry of Na+ triggers an action potential in the postsynaptic neuron.
• Eventually, synaptic communication is terminated when the neurotransmitter is either taken back up into the presynaptic neuron (reuptake) or broken down in the synapse by enzymes

Question 24

Excitatory neurotransmitter

Answer 24

raise the membrane potential towards the critical threshold (membrane potential less negative)

Question 25

inhibitory neurotransmitter

Answer 25

lower the membrane potential away the critical threshold (membrane potential more negative)

Question 26

Summation

Answer 26

the process by which the euron ‘sums up’ all the excitatory and inhibitory signals it receives over a period of time

Question 27

Criteria for transmitter substance

Answer 27

1. Synthesised in the neuron
2. Present at presynaptic terminals, packaged within synaptic vesicles
3. Endogenous substance (drug) at reasonable concentration mimics exactly the action of endogenously released transmitter
4. Specific mechanism exists for removing transmitter from synaptic clef

Question 28

Ionotropic receptors

Answer 28

transmitter binding = direct opening of ion channel
• also termed ligand-gated ion channels
• always stimulatory
• fast – effect lasts a few milliseconds

Question 29

Metabotropic receptors

Answer 29

transmitter binding = indirect activation of Gprotein
• also termed G-protein coupled receptors
• can trigger opening or closing of a separate ion channel & downstream
signalling cascade
• slow – effect takes up to several hours

Question 30

Structure of ionotropic receptors

Answer 30

• Composed of 4 or 5 subunits arranged around a central pore in the membrane
• Receptors can be made up of different combinations of subunits = increase diversity between different tissues
• Examples of ionotropic receptors:
- nicotinic acetylcholine
- GABAA
- glycine
- 5-HT3 receptors

Question 31

Structure of metabotropic receptors

Answer 31

• Composed of a single protein with 7 membrane-spanning regions (α-helices) 
• seven transmembrane (7TM) receptor
• Examples of metabotropic receptors:
   - muscarinic acetylcholine
   - a and b adrenergic receptor
   - all 5-HT receptors except 5-HT3
   - rhodopsin
   - olfactory receptors
   - many others

Question 32

Ionotropic receptors function

Answer 32

• At rest, the channel pore is closed and there is no movement of ions
• Binding of neurotransmitter to its receptor, causes the channel to open
• Ions will flow down their concentration gradient
• Channels will be permeable to anions (e.g. Na+, K+) or cations (Cl-)

Question 33

Metabotropic receptors function

Answer 33

• Binding of neurotransmitter to its receptor causes activation of a G-protein
• The G-protein can act directly on an ion channel, causing the ion pore to open and/or
• The G-protein can activate a second messenger
• Second messenger can bind to and open an ion channel or initiate a signalling cascade (enzymes, gene transcription, etc.)

Question 34

Summary of sequence of events of G protein activation

Answer 34

1. Transmitter binds to receptor
2. GTP exchanges for GDP on the G protein a subunit
3. G protein dissociates from receptor – then ligand as well
4. The 3 subunits (a, b, and g) of the G protein also dissociate
5. The a subunit activates the ion channel
6. The a subunit is inactivated by the hydrolysis of GTP to form GDP (GTPase activity is intrinsic to this subunit)
7. The a subunit recombines with b and g subunits and attaches to the receptor, which can then bind another agonist

Question 35

Second messengers

Answer 35

• G proteins can stimulate (Gs) or inhibit (Gi) enzymes
• Most common enzyme targets:
- adenylate cyclase —> cyclic AMP (cAMP)
- guanylate cyclase —> cyclic GMP (cGMP)
- phospholipase C —> inositol triphosphate (IP3) & diacylglycerol = slow intracellular response